Dermatan sulfate domains defined by the novel antibody GD3A12, in normal tissues and ovarian adenocarcinomas

Dam, Gerdy B. ten; Yamada, Shuhei; Kobayashi, Fumi; Purushothaman, Anurag; Westerlo, Els M.A. van de; Bulten, Johan; Malmström, Anders; Sugahara, Kazuyuki; Massuger, Leon F.A.G.; Kuppevelt, Toin H. Van

doi:10.1007/s00418-009-0592-2

Cited by 30 publications

(25 citation statements)

References 32 publications

(29 reference statements)

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“…Moreover, expression of DSE was found to be altered in laryngeal cancer specimens when compared to normal tissue samples [39]. Significantly, abnormal dermatane sulphate composition has also been reported in both ovarian carcinomas and ovarian cancer cell lines [40], providing further support for a putative role of DSE in our ovarian model.…”

Section: Future Directionsmentioning

confidence: 53%

Molecular signature induced by RNASET2, a tumor antagonizing gene, in ovarian cancer cells

et al. 2011

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Using the Hey3Met2 human ovarian cancer cell line, we previously found the RNASET2 gene to possess a remarkable in vivo tumor suppressor activity, although no in vitro features such as inhibition of cell proliferation, clonogenic potential, impaired growth in soft agar and increase in apoptotic rate could be detected. This is reminiscent of the behavior of genes belonging to the class of tumor antagonizing genes (TAG) which act mainly within the context of the microenvironment. Here we present transcriptional profiles analysis which indicates that investigations of the mechanisms of TAG biological functions require a comparison between the in vitro and in vivo expression patterns. Indeed several genes displaying a biological function potentially related to tumor suppression could not be validated by subsequent in vivo expression analysis. On the other hand the fact that we could find congruency for three genes both in vivo and in vitro adds a warning to a too much stringent categorization of this class of genes which relies on the sensitivity of the methodological approaches.

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Section: Future Directionsmentioning

confidence: 53%

Molecular signature induced by RNASET2, a tumor antagonizing gene, in ovarian cancer cells

et al. 2011

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“…The anti-HS monoclonal antibody JM403 was a kind gift from Johan van der Vlag, Department of Nephrology Radboud University Nijmegen Medical Centre, The Netherlands. Anti-DS single chain variable fragment GD3A12, which recognizes IdoA and sulfated IdoA in DS, was produced and characterized as described in [19]. Rabbit (V4888) anti-tag VSV and the goat anti-mouse FITC-conjugated antibody were from Sigma.…”

Section: Methodsmentioning

confidence: 99%

Iduronic Acid in Chondroitin/Dermatan Sulfate Affects Directional Migration of Aortic Smooth Muscle Cells

et al. 2013

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Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS) proteoglycans that regulate extracellular matrix organization and cell behavior in normal and pathological conditions. A unique feature of CS/DS proteoglycans is the presence of iduronic acid (IdoA), catalyzed by two DS epimerases. Functional ablation of DS-epi1, the main epimerase in these cells, resulted in a major reduction of IdoA both on cell surface and in secreted CS/DS proteoglycans. Downregulation of IdoA led to delayed ability to re-populate wounded areas due to loss of directional persistence of migration. DS-epi1−/− aortic smooth muscle cells, however, had not lost the general property of migration showing even increased speed of movement compared to wild type cells. Where the cell membrane adheres to the substratum, stress fibers were denser whereas focal adhesion sites were fewer. Total cellular expression of focal adhesion kinase (FAK) and phospho-FAK (pFAK) was decreased in mutant cells compared to control cells. As many pathological conditions are dependent on migration, modulation of IdoA content may point to therapeutic strategies for diseases such as cancer and atherosclerosis.

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“…Immunopurified anti-DS-epi1 (2 μg/ml) and anti-GM130 (1:100) antibodies were incubated overnight at 4 °C and visualized using goat anti-rabbit IgG AF488 (Invitrogen A1100) and goat anti-mouse IgG AF546 (Invitrogen A11003), respectively, at 1:200 dilutions. The presence of IdoA on the cell surface was visualized using a single chain phage display antibody (GD3A12) that specifically recognizes DS (18). Cells were fixed with methanol for 2 min and stained as previously described by Li et al , 2008 (9).…”

Section: Methodsmentioning

confidence: 99%

Dermatan Sulfate Is Involved in the Tumorigenic Properties of Esophagus Squamous Cell Carcinoma

et al. 2012

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Extracellular matrix, either produced by cancer cells or by cancer-associated fibroblasts, influences angiogenesis, invasion and metastasis. Chondroitin/dermatan sulfate (CS/DS) proteoglycans, which occur both in the matrix and at the cell surface, play important roles in these processes. The unique feature that distinguishes DS from CS is the presence of iduronic acid (IdoA) in DS. Here, we report that CS/DS is increased five-fold in human biopsies of esophagus squamous cell carcinoma (ESCC), an aggressive tumor with poor prognosis, as compared with normal tissue. The main IdoA-producing enzyme, DS epimerase 1 (DS-epi1), together with the 6-O- and 4-O-sulfotransferases, were highly up-regulated in ESCC biopsies. Importantly, CS/DS structure in patient tumors was significantly altered compared with normal tissue, as determined by sensitive mass spectrometry. To further understand the roles of IdoA in tumor development, DS-epi1 expression, and consequently IdoA content, was downregulated in ESCC cells. IdoA-deficient cells exhibited decreased migration and invasion capabilities in vitro, which was associated with reduced cellular binding of hepatocyte growth factor, inhibition of pERK-1/2 signaling, and de-regulated actin cytoskeleton dynamics and focal adhesion formation. Our findings demonstrate that IdoA in DS influences tumorigenesis by affecting cancer cell behavior. Therefore, down-regulation of IdoA by DS-epi1 inhibitors may represent a new anti-cancer therapy.

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Dermatan sulfate domains defined by the novel antibody GD3A12, in normal tissues and ovarian adenocarcinomas

Cited by 30 publications

References 32 publications

Molecular signature induced by RNASET2, a tumor antagonizing gene, in ovarian cancer cells

Molecular signature induced by RNASET2, a tumor antagonizing gene, in ovarian cancer cells

Iduronic Acid in Chondroitin/Dermatan Sulfate Affects Directional Migration of Aortic Smooth Muscle Cells

Dermatan Sulfate Is Involved in the Tumorigenic Properties of Esophagus Squamous Cell Carcinoma

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